Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma

This study was undertaken to determine the validity of Fuhrman grading in a series of papillary renal cell carcinomas (PRCCs), to examine the interrelationship and prognostic significance of the individual components of the grading system, and further to determine whether any observed predictive value was independent of other prognostic indicators. Ninety cases of PRCC were studied. Fifty-nine tumors were of type 1 and 31 were of type 2. There were 33 TNM stage 1, 26 stage 2, 18 stage 3, and 12 stage 4 tumors, whereas division of cases according to pT category showed 14 pT1a, 20 pT1b, 25 pT2, 15 pT3a, 4 pT3b, and 11 pT4 tumors. Ten tumors were grade 1, 58 grade 2, and 22 grade 3 when predominant Fuhrman grade was assigned, whereas grading according to the high-power field containing the highest grade (focal grade) showed 40 grade 2, 49 grade 3, and 1 grade 4 tumors. Measurements of nuclear size (area, major axis, perimeter) and shape (shape factor, compactness) were undertaken using image analysis. Nuclear area ranged from 27.63 to 116.39 microM, major axis length 6.70 to 14.06 microM, and nuclear perimeter 20.05 to 41.77 microM. Shape factor ranged from 0.805 to 0.878 and compactness from 14.33 to 15.66. Predominant nucleolar grade using the criteria of the Fuhrman classification was nucleolar grade 1 for 13 tumors, nucleolar grade 2 for 56 tumors, and nucleolar grade 3 for 21 tumors. Focal nucleolar grade based on the high-power field showing the greatest degree of nuclear pleomorphism, was grade 2 for 38 tumors and grade 3 for 52 tumors. pT category, TNM stage, focal Fuhrman grade, and PRCC type were significantly associated with survival. Of the various measures of the components of the Fuhrman classification, only focal nucleolar grade was associated with survival, on univariate analysis. On multivariate analysis, focal nucleolar grade and tumor diameter were independently associated with survival, whereas TNM stage retained significance independent of other parameters. It is concluded that assessment of nucleolar prominence rather than Fuhrman grade is applicable for stratification of tumors within TNM stage or pT category for PRCC and that this should be based upon the high-power field showing the greatest degree of nuclear pleomorphism.     

Prognostic significance of matrix metalloproteinases-2 activation ratio in renal cell carcinoma

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMP-2 and MMP-9 have been reported to be closely associated with tumor invasion and metastasis in various human carcinomas. METHODS: Tissue samples were obtained from 57 patients with renal cell carcinoma (RCC) who underwent radical nephrectomy in our hospital. We examined the expression of MMPs by gelatin zymography and assessed correlations with clinico-pathological parameters and clinical outcomes. RESULTS: We detected bands corresponding to MMP-9, proMMP-2 and active MMP-2. The expression of active MMP-2 and MMP-2 activation ratio (active MMP-2/[proMMP-2 and active MMP-2]) were higher in T3 tumors than in T1 and T2 tumors. There were no significant differences in the expression of proMMP-2, active MMP-2 or MMP-9 for any of the clinico-pathological parameters. Patients with high MMP-2 activation ratio or high MMP-9 had significantly worse cause-specific survival. Interestingly, among patients with stage III RCC, those with high MMP-2 activation ratio or high active MMP-2 had significantly worse cause-specific survival. Univariate analysis showed that histological grade (P = 0.0001), histologic type (P = 0.0005), MMP-2 activation ratio (P = 0.0159), stage (P = 0.0001), MMP-9 (P = 0.0316), and T (primary tumor) category of TNM (primary tumor, lymph node, metastasis) classification (P = 0.0021) were significant predictors of clinical outcome. Multivariate analysis showed that only histological grade (P = 0.002) and stage (P = 0.0099) were independently significant predictors of clinical outcome. CONCLUSION: Activation of MMP-2 appears to play important roles in initiating metastasis, as shown by results obtained with stage III RCC patients. However, further study is needed to confirm this.     

Evaluation of the 1997 tumour, nodes and metastases classification of renal cell carcinoma: experience in 172 patients

OBJECTIVE: To compare the prognostic relevance of the 1987 and 1997 tumour, nodes and metastases (TNM) systems for staging renal cell carcinoma (RCC) in predicting patient outcome. PATIENTS AND METHODS: A series of 172 consecutive patients with RCC who underwent radical nephrectomy from January 1990 to October 1997 was evaluated comparatively according to the 1987 and 1997 TNM classifications. The median (range) follow-up of the patients was 50 (19-112) months. The probability of survival was estimated by the Kaplan-Meier method, using the log-rank test to estimate differences among levels of the analysed variables. RESULTS: Using the 1997 TNM classification resulted in a redistribution of 99 patients from stage pT2 on the 1987 TNM classification to stage pT1. As the staging criteria for pT3 and pT4 did not change, there was no re-classification of these patients. Kaplan-Meier survival curves showed a similar separation in 5-year survival between stage pT1 and pT2 using both systems; 100% vs 80% for the 1987 TNM and 86% vs 69% for the 1997 TNM systems. This difference in survival rates between patients with pT1 and pT2 disease was statistically significant only for the 1997 TNM staging system. However, when the 1987 TNM staging classification was applied, the separation in 5-year survival rates between pT2 and pT3 disease was greater. CONCLUSION: This study confirms the prognostic relevance of the 1987 TNM system, as established in the present patients. The 1997 TNM classification resulted in a better stratification of patients with pT1-pT2 disease, but had similar prognostic value for pT2 and pT3 disease.     

Histological subtyping and nuclear grading of renal cell carcinoma and their implications for survival: a retrospective nation-wide study of 629 patients

OBJECTS: The aim of this study was to evaluate the prognostic significance of the current WHO histological subtyping and Fuhrman nuclear grading on the survival of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective population-based study was carried out on all patients with a histopathologically confirmed diagnosis of RCC in Iceland between 1971 and 2000. Fuhrman grade, TNM stage, and survival were evaluated and multivariate analysis applied in order to determine prognostic factors. RESULTS: Out of 629 patients (387 males, 242 females, mean age 64 years), 558 (88.7%) had clear cell, 53 (8.4%) papillary, and 13 (2.1%) chromophobe RCC. Patient demographics were comparable for the two major subtypes, but chromophobe RCCs were larger in size and were diagnosed at a younger age. Clear cell RCCs were more often of higher grades (G3+G4, 48.4%) and at advanced TNM stages (III+IV, 59.3%) than papillary RCCs (22.6% and 34% respectively, p<0.001). Linear regression analysis showed a strong correlation between grade, tumor size, and stage (p<0.001). Chromophobe RCCs had a better survival in univariate analysis than both papillary and clear cell RCCs (84.6% vs. 66.5% and 54.9% 5-year disease specific survival, p<0.001). However, in the multivariate analysis, only the patient's age, calendar year of diagnosis, TNM stage, and nuclear grade were independent prognostic factors of survival. CONCLUSION: In this complete nation-wide series nuclear grading is important in predicting survival of patients with RCC. It is strongly related to both tumor size and stage, with stage being by far the strongest prognostic factor. Different histological subtypes confer different survival. However, in spite of the distinctive cytogenetic and molecular characteristics of the subtypes, the survival difference is to a large extent due to differences in grade and particularly stage.     

Survival analysis for localized renal cell carcinoma. Prognostic value of 1997 TNM classification

Backgroundthe 5th edition of TNM classification for renal cell carcinoma changed the cut-off point of the tumor size for localized tumors, achieving a better distribution of patients with similar survival. Nevertheless, because of the variable evolution of renal cell carcinoma, the prognostic significance of tumor size is questioned as a staging criterion in organ-confined renal cell carinoma. We analyse renal cell carcinoma specific survival and the prognostic significance of tumor size in I and II stage.MethodsWe made a retrospective study with 158 renal cell carcinoma surgically treated in our hospital along 12 years. It was created a data base with clinical variables from patient and tumor and analyzed pathological staging, nuclear grade and specific survival, overall stage I and II.Results27 renal cell carcinoma were pT1 (17.08%), 52 pT2 (32.91%), 45 pT3A (28.45%), 10 pT3B (6.32%), y 24 pT4 (15.18%). The specific survival at 5 years for pT1-pT2, I-II stage, was 100% and 94% respectively, and no statistic significant differences were found between stage I and II (log-rank test 0.53, p>0.05). The specific survival at 5 years for pT3A, pT3B, y pT4 was 76.5%, 66.6% y 38.4%. There was a significant difference in survival in accordance with the tumor location, intrarenal (T1 y T2) versus extrarenal (T3A, T3B, T4) (log-rank test 9.06, p < 0.05). According to nuclear grade we don’t find significant differences for pT1 y pT2 (Fisher test, p=1). Regarding the relation between pT stage and nuclear grade of the tumor we obtained a ?2 inear tendency of 38.19, p < 0.001.ConclusionThe differences in the evolution of the organ-confined renal cell carcinoma with respect to the tumor size may be due to other molecular and biological variables, probably associated with stage. not controlled in essays. The TNM classification for organ-confined renal cell carcinoma based in tumor size seems artificial. New revisions of the classification system are necessary to identify which organ-confined carcinoma will have unfavourable evolution and to include them in a different category.     

pT1 substaging in renal cell carcinoma: validation of the 2002 TNM staging modification of malignant renal epithelial tumors

PURPOSE: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. MATERIALS AND METHODS: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. RESULTS: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p = 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p = 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p = 0.001 and 5.49, p = 0.001) and for the CRCC subtype (RR 5.50, p = 0.001 and 5.18, p = 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p = 0.001). All statistical analyses were adjusted for age and sex. CONCLUSIONS: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.     

Clinicopathological factors predicting recurrence of N0M0 renal cell carcinoma: A case series analysis of one facility

BACKGROUND: Although many factors have been reported as predictors of the recurrence of renal cell carcinoma (RCC), none of the factors are consistent among different studies. In the study presented here, the potential clinicopathological predictors of the recurrence of N0M0 RCC were examined. METHODS: A total of 201 patients who underwent nephrectomy for N0M0 RCC were examined to determine the pathological tumor stage (pT stage), pathological tumor grade of malignancy (tumor grade), symptoms, and tumor size. RESULTS: RCC recurred in 29 patients (14.4%), 50% of whom developed new tumors within 24 months after nephrectomy. The disease-free 3- and 10-year survival rates declined as the pT stage and tumor grade increased: these rates were, respectively, 98.6% and 86.5% for pT1a; 93.7% and 87.9% for pT1b; 100% and 100% for pT2; 78.6% and 58.0% for pT3a; and 88.9% and 16.7% for pT3b. Significant differences in the recurrence rate were noted between pT3 and pT1 or pT2, as well as between grade 3 disease and grade 1 or grade 2 tumors. Multivariate analysis showed that a combination of the pT stage, grade, and presence of symptoms was useful for predicting the recurrence of RCC. CONCLUSION: The present study showed that patients undergoing nephrectomy for N0M0 RCC should be followed-up carefully for 2 years postoperatively with special attention to high pT stage, high grade, and the development of symptoms.     

A clinical investigation on renal pelvic and ureteral tumors

The 60 cases of primary renal pelvic and ureteral tumors treated at Mie University hospitals between January 1977 and December 1987 were reviewed and factors predicting the prognosis were investigated. The patients consisted of 47 men and 13 women (3.6: 1.0). Their ages ranged from 38 to 82 years with a mean of 65.2 years. According to Akaza's category classification of the ureteropelvic tumor, 42 cases were classified to category A, 15 cases category B and 1 case was classified to category C. Histologically, 59 transitional cell carcinomas and 1 squamous cell carcinoma were found. As to grading, 5 was G1, 31 G2, 21 G3 and 2 GX. As to staging, 20 were pT1, 10 pT2, 21 pT3, 3 pT4 and 6 pTX. Staging was correlated well with grading. Total nephroureterectomy with bladder cuff was performed on 39 patients and the other surgical treatments were done on 15 patients. Recurrence of the bladder tumor was found in 22.4%. The 5-year survival rate (Kaplan-Meier's method) was 47.8% for all of the patients. Among the patients with transitional cell carcinoma, the 5-year survival rate was 100% for G1, 57.6% for G2 and 28.6% for G3. As to staging the 5-year survival rate was 90.0% for below pT1, 20.0% for pT2 and 41.1% for pT3. The results from the present study suggest the prognosis is decided by grade and stage in pelvic and ureteral tumors, and it is wanted to develop a system of postoperative adjuvant therapy.     

Chromophobe renal cell carcinoma: the impact of tumor grade on outcome

It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC). The objective of this study was to determine whether nucleolar grading and the recently described chromophobe RCC grading system by Paner and colleagues provide prognostic information. Pathologic features of 185 patients with chromophobe RCC treated surgically between 1970 and 2006 were reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer-specific (CS) survival was estimated using the Kaplan-Meier method, and associations with CS survival were evaluated using Cox proportional hazard regression models. Twenty-three patients died from RCC at a mean of 3.0 years after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15 years after surgery. Univariate associations with CS survival included the 2010 TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis, chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features remained significantly associated with CS survival after adjusting for the 2010 TNM stage groupings. When the analysis was restricted to the 155 patients with nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping (I vs. II) was significantly associated with CS survival (P=0.03). Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed.     

Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases

The aggregate literature suggests that chromophobe renal cell carcinoma (RCC) is biologically a tumor of low malignant potential with reported 5-year and 10-year survival rates of 78% to 100% and 80% to 90%, respectively. The conventional prognostic parameters that determine the outcome of the tumors that progress remain to be fully characterized. Clinicopathologic features of 145 cases were correlated with outcome. The mean age of the patients was 59 years (range, 27 to 82) and the male to female ratio was 1.1:1. Most tumors were well circumscribed and averaged 8.0 cm (range, 1.0 to 30.0 cm); multifocality and bilaterality were present in 8% and 3% of patients. Sixty (41%) were eosinophilic variant (greater than 80% eosinophilic cells), 18 (12%) were classic type (greater than 80% pale cells), and 67 (46%) were mixed (containing variable admixture of pale and eosinophilic cells). A subset of eosinophilic chromophobe RCC contained or had areas similar to renal oncocytomas. These tumors tended to be more commonly bilateral (11%) and multifocal (22%) and were not associated with necrosis or sarcomatoid change. Sarcomatoid change was present in 12/145 (8%) tumors. By histologic grade, 1%, 19%, 74%, 6% were Fuhrman nuclear grade 1, 2, 3, and 4. Nineteen percent, 21%, 28%, 13%, 4%, 1%, and 3% were pT (2002) stage pT1a, pT1b, pT2, pT3a, pT3b, pT3c, and pT4 tumors. Two percent tumors were pN1 at presentation and 2.8% tumors were M1 at presentation. Follow-up (1 to 182 mo, mean 48 mo, median 37 mo) was available in 123 cases. Disease progression (local recurrence 4, metastasis 15, and/or death 10) was seen in 20 patients. In univariable analysis, tumor size (P=0.025), pT stage (P<0.001), broad alveolar architecture (P=0.012), Fuhrman nuclear grade (P<0.001), microscopic tumor necrosis (P=0.001), vascular invasion (P=0.020), and sarcomatoid change (P< or =0.001) were associated with progression. A multivariable Cox regression model revealed sarcomatoid change (P=0.013, estimated relative hazard 4.7), microscopic necrosis (P=0.020, relative hazard=3.5), and pT stage (P=0.025, relative hazard 3.4) as independent predictors of aggressive chromophobe RCC. Although the large majority of chromophobe RCCs have a favorable prognosis, a distinct subset of patients progress. The pT stage of tumor, tumor necrosis, and sarcomatoid change all predict aggressive phenotype of chromophobe RCC. The adverse presence of these features in a nephrectomy specimen with chromophobe RCC warrants active surveillance, and these patients may be candidates for adjuvant therapies as they become available.     

Adjuvante autologe Tumorvakzine beim Nierenzellkarzinom

Background

Organ-confined renal cell carcinoma (RCC) is associated with tumour progression after surgical therapy in approximately 30% of cases. However, of all recently available adjuvant treatment options, only the autologous tumour cell lysate vaccination therapy (Reniale) has been able to demonstrate a significant positive impact on progression-free survival in a phase III trial. Nevertheless, this therapeutic option has not yet been established as a standard adjuvant treatment.

Materials and methods

Between August 1993 and December 1996, a total of 1,267 patients who underwent radical tumour nephrectomy at 84 German centres received Reniale outside a controlled trial. Of these patients, 692 presented at stage pT2–3, pNx-2, M0 (based on the 4th version of TNM classification). These patients were matched with a cohort of 861 patients not receiving any adjuvant treatment who underwent surgical therapy for RCC in a 15-year period in the Carl-Thiem-Klinikum in Cottbus, Germany. Matching criteria included age, gender, pT stage, pN stage, grading, histological cell type, and UICC stage. This resulted in 495 matched pairs (study group n=990) that were comparable regarding demographic and tumour-specific criteria. Statistical analyses included univariate and multivariate analyses of overall survival (OS). Median follow-up time of all patients still alive at the end of the trial (n=667) was 11 years.

Results

In the vaccine group, OS after 5 and 10 years was 80.6% and 68.9%, respectively, whereas control patients had an OS of 79.2% and 62.1%, respectively (p=0.066). The 5-year OS of patients with pT3 RCC was 71.3% after vaccination therapy and 65.4% for control patients. After 10 years, 53.6% of the patients in the vaccine group and 36.2% in the control group were still alive (p=0.022). Median survival of patients with pT3 RCC was 81 months (SD 7.8) in the control group. This period was not achieved in the vaccine group. Multivariate Cox analysis revealed a significant positive impact of Reniale on OS among the whole study group [hazard ratio (HR) 1.28, p=0.030]. The analysis of patient subgroups showed a significant positive influence of Reniale for patients presenting with pT3 tumours (HR 1.67, p=0.001).

Conclusion

Adjuvant postsurgical treatment with Reniale in patients presenting with stage pT3 RCC results in a significant enhancement of OS and should be considered especially in this group of patients. Further clinical trials integrating the recent TNM classification and comprising different risk constellations should follow in order to ultimately assess the value of adjuvant treatment with vaccination immunotherapy.     

Das Nierenzellkarzinom

Due to the increasing epidemiological importance of renal cell carcinoma (RCC) in the past, several studies have been undertaken to evaluate a variety of parameters in view of their aptitude for reliably predicting individual prognosis. Currently, staging according to the TNM classification and pathohistological nuclear grading of the tumor is most widely used for determining prognosis. In the latest edition of the TNM system, a subdivision of the stage pT1 into the stages pT1a and pT1b has been established. Analyzing a total of 129 patients with a postoperative follow-up period of 60 months after radical nephrectomy, we investigated the TNM classification in regard to its prognostic potential with emphasis on the new subdivision of the stage pT1. Furthermore, the results were compared to Störkel’s prognostic score, which was first described in 1990 as a useful tool for predicting individual prognosis in patients with RCC. In conclusion, our study demonstrates that subdivision of the stage pT1 into the stages pT1a and pT1b did not result in any improvement concerning the aptitude of the TNM classification to predict individual prognosis. In comparison, Störkel’s prognostic score has statistically proven to be superior to the TNM classification in regard to its prognostic potential. According to our experience, determination of Störkel’s prognostic score can be easily performed by the pathologist without much expense in the course of daily routine diagnostic procedures. Therefore, we strongly recommend Störkel’s prognostic score as the parameter of choice to reliably predict individual prognosis of patients suffering from RCC.     

Is There a Need to Further Subclassify pT2 Renal Cell Cancers as Implemented by the Revised 7th TNM Version?

Background

The recently modified TNM classification of renal cell carcinoma (RCC) (7th edition) has implemented a subdivision of pT2 tumours into stage pT2a (>7 or ≤10 cm) versus pT2b disease (>10 cm).

Objective

Our aim was to evaluate whether this subdivision of pT2 RCC is justified due to a clinical prognosis divergence between the two groups (pT2a vs pT2b)

Design, setting, and participants

In total, 5122 patients were subjected to either radical nephrectomy or nephron-sparing surgery at three centres in Germany (University Hospitals of Hannover, Homburg/Saar, and Marburg). Patients were reclassified into stage pT2a and pT2b according to the maximum tumour diameter as suggested by the 7th revised version of the TNM classification system.

Measurements

The t test and Fisher exact test were applied to evaluate the comparability of the two groups (pT2a vs pT2b) regarding several additional patients’ and tumour-specific characteristics of known prognostic relevance for RCC. Univariable (Kaplan-Meier analysis) and multivariable statistical analyses (Cox proportional hazards regression model) were applied to identify a possible difference between the two groups (pT2a vs pT2b) regarding cancer-specific survival (CSS).

Results and limitations

Applying the new TNM classification, 579 previously pT2-staged patients were divided into 445 (76.9%) with pT2a and 134 (23.1%) with pT2b tumours. Kaplan-Meier curves revealed no significant difference in CSS between pT2a and pT2b patients; 5-yr CSS was 79.0% and 74.1%, respectively (p = 0.38). When applying multivariable analysis, unlike tumour grade and N/M status, pT2 subclassification failed to independently predict survival in RCC patients.

Conclusions

The new subclassification of pT2 RCC into two different subgroups as suggested by the latest modification of the TNM system does not yield additional/prognostic information.     

SHOULD DIRECT IPSILATERAL ADRENAL INVASION FROM RENAL CELL CARCINOMA BE CLASSIFIED AS pT3a?

PURPOSE: The 2002 American Joint Committee on Cancer primary tumor classification for renal cell carcinoma (RCC) defines a tumor as pT3a if it invades the perinephric or renal sinus fat or directly invades the ipsilateral adrenal gland. In the current study we evaluated the association of direct ipsilateral adrenal invasion with outcome to determine if reclassification of these tumors as pT4 would improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 424 patients who underwent nephrectomy and adrenalectomy for unilateral, sporadic, pT3 or pT4 RCC between 1970 and 2000 at the Mayo Clinic. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: Cancer specific survival for the 22 patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland was significantly worse compared with that of patients with pT3a (p <0.001) or pT3b (p = 0.011) disease that did not invade the adrenal gland. There was no significant difference in the 5-year cancer specific survival between the patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland and patients with pT4 tumors (cancer specific survival rates of 20% and 14%, respectively, p = 0.490). CONCLUSIONS: Although rare, RCC with direct ipsilateral adrenal invasion behaves more aggressively than tumors involving perinephric or renal sinus fat. We believe that RCC tumors with direct adrenal invasion should be classified as pT4.     

Prognostic impact of tumor size on pT2 renal cell carcinoma: an international multicenter experience

PURPOSE: The current tumor classification for renal cell carcinoma classifies pT2 tumors as larger than 7 cm in greatest dimension and limited to the kidney. We examined the current pT2 tumor classification of renal cell carcinoma and determined whether a tumor size cutoff exists that would improve prognostic accuracy. MATERIALS AND METHODS: We studied 706 patients with pT2 renal cell carcinoma treated with surgical extirpation at 9 international academic centers. Data collected from each patient included age at diagnosis, gender, 2002 TNM (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status, histological subtype and disease specific survival. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median followup was 52 months. Univariate Cox regression analysis showed a significant association of tumor size with disease specific survival (HR 1.11, p<0.001). An ideal tumor size cutoff of 11 cm was identified, which led to the stratification of 2 groups with respect to disease specific survival (p<0.0001) with 5 and 10-year survival rates of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm, respectively. The incidence of metastases was significantly greater in the larger than 11 cm group, while Eastern Cooperative Oncology Group performance status, Fuhrman grade and histological subtype were similar. Multivariate Cox regression analysis retained tumor size as an independent prognostic factor and as the strongest prognostic factor for patients with pT2N0M0 disease. CONCLUSIONS: Our data suggest that the current pT2 classification can be improved by subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm. Patients in the proposed pT2bN0M0 group are at higher risk for death from renal cell carcinoma and should be considered for adjuvant therapies. External validation is warranted before suggesting change to the TNM classification.     

Prognostic value of renal cell carcinoma nuclear grading: multivariate analysis of 333 cases

OBJECTIVE: To evaluate the independent predictive value of the nuclear grading system according to Fuhrman in relation to the disease-specific survival of patients with renal clear cell carcinoma. MATERIAL AND METHODS: 333 patients who underwent radical nephrectomy for renal clear cell carcinoma between 1983 and 1999 were evaluated. In all patients we retrospectively studied nuclear grading, average tumor size, multifocality, pathologic stage of primary tumor, vein invasion, lymph node involvement and distant metastases. The Kaplan-Meier method was applied to evaluate disease-specific survival rates. The log rank test was used to compare survival curves and for univariate analysis. The Cox proportional hazards model was used for the multivariate analysis. RESULTS: Histologic grade was G1 in 83 cases (25%), G2 in 117 cases (35%), G3 in 110 cases (33%) and G4 in 23 cases (7%). Our data showed that nuclear grading according to Fuhrman is related to medium tumor size (p < 0.0001), pathologic stage of cancer (p < 0.001), venous system invasion (p < 0.001), lymph node involvement (p < 0.001) and distant metastases (p < 0.001). The disease-specific survival after 5 and 10 years was 94 and 88%, respectively, in patients with G1, 86 and 75% in patients with G2, 59 and 40% in patients with G3 and 31% in patients with G4 (log rank p value < 0.0001). Multivariate analysis showed that nuclear grading by Fuhrman has a prognostic independent predictive value (hazard ratio = 1.8461, p = 0.002). CONCLUSIONS: Nuclear grading is an important independent predictive factor of disease-specific survival in patients with renal cell carcinoma.     

Microscopic venous invasion: a prognostic factor in renal cell carcinoma

OBJECTIVE: Microscopic venous invasion (MVI) is characterized by local destruction of the endothelium by a tumor. The prognostic value of MVI in renal cell carcinoma (RCC) is not well established. MATERIALS AND METHODS: From 1980 until 1990, 255 patients (169 men and 86 women), aged 16-87 (mean 60) years were treated by radical nephrectomy for N0M0 RCC. There were 9 pT1, 163 pT2, 30 pT3a, 34 pT3b, and 19 pT3ab (TNM 1992). The median follow-up time was 74 months. MVI was determined by a double-blind histological study with immunohistochemical staining. RESULTS: MVI was noted in 74 patients (29%). MVI significantly increased metastatic progression (p = 0.003). Only stage and Fuhrman's grade were significant factors for metastatic progression in a multivariate analysis. MVI decreased the actuarial survival rates at 1 year (p = 0.01), but not significantly at 5 and 10 years. MVI and non-MVI survival curves were statistically different with the Peto/Wilcoxon (p = 0.04) and Gehan/Wilcoxon (p = 0.03) tests, but not with the log rank test (p = 0.06). MVI decreased survival in cases with a tumor size of 10 cm or more, capsular invasion, macroscopic venous invasion, stage pT3ab, sarcomatoid cell carcinoma and Fuhrman's grade IV. Only the stage was a significant factor for survival in a multivariate analysis. CONCLUSION: In RCC, MVI is related to cancer progression and survival, but probably not as an independent prognostic factor.     

Incidental detection beyond pathological factors as prognostic predictor of renal cell carcinoma

PURPOSE: To evaluate the prognostic significance of different detection modalities of renal cell carcinoma (RCC) in a large cohort of patients who had been previously submitted to surgery in two teaching hospitals in Italy. MATERIALS AND METHODS: We reviewed the clinical records of 1446 patients who had been submitted to surgical treatment for RCC at the Departments of Urology of Padua (n=747) and Verona (n=699) from 1976 to 2000. Patients were classified into two groups according to the detection mode: symptomatic and incidental. The cancer-specific survival probability was estimated according to the Kaplan-Meier method. In order to compare the survival curves the log rank test was used. The predictive independent value of the variables was examined using the Cox proportional hazards model. RESULTS: Six hundred and thirty patients (43.6%) were treated for incidental RCC and 816 (56.4%) for symptomatic RCC. In the incidental group, the size (p<0.001), the pathological stage (p<0.001) and the nuclear grading (p<0.001) of tumors were lower than those causing symptoms. The 5-year and 10-year cancer-specific survival probability were 84% and 75% in the incidental group, and 66% and 54.5% in the symptomatic group (p<0.0001), respectively. At a multivariate analysis, the mode of detection was an independent predictive variable (H.R. 1.559), as well as pathological stage (H.R. 1.809), nuclear grading (H.R. 1.411), size 相似文献   

A new staging system for locally advanced (pT3-4) renal cell carcinoma: a multicenter European study including 2,000 patients

PURPOSE: We provide an adequate prognostic stratification for locally advanced renal cell carcinoma and propose a new TNM classification. MATERIALS AND METHODS: We analyzed clinical and pathological data on a large series of patients undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 12 European centers. Cancer specific survivals were estimated using the Kaplan-Meier method. The log rank test was used for comparing survival curves and for univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The analysis included 1,969 patients. Median survivor followup was 49 months. Five-year cancer specific survival was 60% for pT3a, 46.2% for pT3b, 10% for pT3c and 12% for pT4 tumors (p <0.0001). According to median survival we identified 3 prognostic groups, including 1--patients with renal vein thrombosis (117 months), fat invasion (98 months) or infradiaphragmatic vena caval thrombosis (67 months), 2--patients with adrenal invasion alone (24 months), renal vein thrombosis plus fat invasion (24 months) or infradiaphragmatic vena cava plus fat invasion (24 months) and 3--patients with renal or infradiaphragmatic caval thrombosis plus adrenal involvement (11 months), supradiaphragmatic vena caval thrombosis (12 months) or Gerota's fascia invasion (12 months). Five-year cancer specific survival rates in groups 1 to 3 were 61%, 35% and 12.9%, respectively (p <0.0001). On multivariate analysis the proposed classification had an independent prognostic value. CONCLUSIONS: Our results suggest the necessity of reclassifying locally advanced renal cell carcinoma according to the 3 described prognostic categories.     

Simple enucleation for the treatment of renal cell carcinoma between 4 and 7 cm in greatest dimension: progression and long-term survival

PURPOSE: We present our findings in a series of patients treated with simple enucleation for RCC 4 to 7 cm in greatest dimension. We specifically report the incidence of local and systemic recurrence, and the disease specific survival rate. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on 71 patients who underwent nephron sparing surgery by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed, 4 to 7 cm RCC. Patients with a solitary kidney due to previous RCC treated with radical nephrectomy were excluded from study. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free of distant metastases before surgery (M0). Patient status was last evaluated in May 2005. Mean followup was 74 months (median 51, range 12 to 225). RESULTS: Pathological review according to the 2002 TNM classification showed that 42% of the tumors (30 of 71) were pT1a, 44% (31 of 71) were pT1b and 14% (10 of 71) were pT3a. Mean tumor greatest dimension +/- SD was 4.7 +/- 0.81 cm (median 4.5, range 4.0 to 7.0) cm. None of the patients died within the first 30 days of surgery. There were no major complications requiring open reoperation, such as bleeding and urinary leakage/urinoma. Five and 8-year cancer specific survival was 85.1% and 81.6%, respectively. Five-year cancer specific survival in patients with pT1a (4 cm), pT1b and pT3a disease was 95.7%, 83.3% and 58.3%, respectively (pT1a vs pT1b p = 0.254, pT1a vs pT3a p = 0.006 and pT1b vs pT3a p = 0.143). Overall 10 patients experienced progressive disease (14.9%), of whom 3 had local recurrence (4.5%) alone or local recurrence associated with distant metastases. CONCLUSIONS: Simple tumor enucleation is a useful and acceptable approach to nephron sparing surgery for 4 to 7 cm RCC. It provides long-term cancer specific survival rates similar to those of radical nephrectomy and is not associated with a greater risk of local recurrence than partial nephrectomy for RCC less than 4 cm in greatest dimension.